Abstract: Compositions and methods for the therapy and diagnosis of cancer, such as prostate cancer, are disclosed. Compositions may comprise one or more prostate-specific proteins, immunogenic portions thereof, or polynucleotides that encode such portions. Alternatively, a therapeutic composition may comprise an antigen presenting cell that expresses a prostate-specific protein, or a T cell that is specific for cells expressing such a protein. Such compositions may be used, for example, for the prevention and treatment of diseases such as prostate cancer. Diagnostic methods based on detecting a prostate-specific protein, or mRNA encoding such a protein, in a sample are also provided.

Abstract: The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of lung cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of lung tumor cells and methods of using the same to prevent or inhibit metastasis of lung tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic lung cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic lung cancer by assaying for the presence of an aberrant form of uteroglobin.

Abstract: Nucleic acid constructs for expressing an effector gene, with the nucleic acid construct comprising a promoter I (component a) which controls the expression of a transcription factor gene (component b), a transcription factor gene (component b), a promoter II (component c) to which the gene product of the transcription factor gene binds and which controls the expression of an effector gene (component d), and effector gene (component d), wherein the activity of the gene product of the transcription factor gene depends on one or more cellular regulatory proteins which bind to this gene product and affect its activity, and isolated cells containing the nucleic acid constructs, can be used for preparing a drug for treating diseases and in methods of treating diseases.

Abstract: A method for the preparation of selected phosphopeptides having anticariogenic and other activities, comprising the steps of completely digesting a soluble monovalent cation salt of casein in solution with a proteolytic enzyme, adding a mineral acid to the solution to adjust the pH to about 4.7, removing any precipitate produced, adding CaCl2 to a level of about 1.0% w/v to cause aggregation of at least the selected phosphopeptides in said digested solution, separating the aggregated phosphopeptides from the solution through a filter having a molecular weight exclusion limit lying substantially within the range 10,000 to 20,000 while passing the bulk of the remaining phosphopeptides and solution, diafiltering the separated phosphopeptides with water through a filter and concentrating and drying the retentate.

Abstract: A human CD2 cytoplasmic tail binding protein, CD2BP1, is described, as well as the nucleic acids encoding the protein. Also described are expression vectors and recombinant host cells comprising nucleic acids encoding the CD2BP1 protein, and methods of use for the CD2BP1 protein and nucleic acids encoding the CD2BP1 protein.

Abstract: The present invention relates to a polypeptide composition effective to alter the activity of a first protein that interacts with a second protein, where the second protein contains at least one WD-40 region. The polypeptides of the present invention typically have between 4 and 50 amino acids whose sequence is the same as a sequence of the same length in the WD-40 region of the second protein. The invention further includes a method of altering the activity of the above described first protein. In one embodiment of the invention the polypeptide composition is effective to alter the activity of a protein kinase C, where the protein kinase C interacts with a second protein, and the second protein contains at least one WD-40 region (e.g., RACK1).

Abstract: The method and compositions of this invention provide an effective and reliable substitute for the currently employed ICA assay for diabetes. By providing a method for detecting autoantibodies to both GAD65 and IA-2 auto-antigens, the method provides a chemical assay which has improved reliability. In addition, these antigens may be employed in therapeutic regimens aimed at achieving immune tolerance and therefore amelioration of the clinical condition.

Abstract: The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of lung cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of lung tumor cells and methods of using the same to prevent or inhibit metastasis of lung tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic lung cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic lung cancer by assaying for the presence of an aberrant form of uteroglobin.

Abstract: The present invention relates generally to a newly identified adaptor protein FRS2 and related products and methods. FRS2 links protein kinases to activating partners in cells. The invention also relates to nucleic acid molecules encoding portions of FRS2, nucleic acid vectors containing FRS2 related nucleic acid molecules, recombinant cells containing such nucleic acid vectors, polypeptides purified from such recombinant cells, antibodies to such polypeptides, and methods of identifying compounds that enhance or block FRS2 interactions with natural binding partners. Also disclosed are methods for diagnosing abnormal conditions in an organism with FRS2 related molecules or compounds.

Abstract: Phosphopeptides which significantly reduce bone loss or weakening are provided by the invention. Also provided is a method for treating or preventing any condition associated with bone loss or weakening by administering the phosphopeptides by oral or injectable means.

Abstract: The present invention relates to two Sam68-like mammalian proteins, namely SLM-1 and SLM-2, and nucleic acid molecules encoding them. The invention also relates to expression vectors and cells capable of expressing the proteins and antibodies capable of specifically binding to the proteins. Kits for the assay of tyrosine kinase activity are discussed which may be used to determine whether or not a cell is cancerous. The present invention further relates to transgenic animals such as “knockout mice”. Knockout mice may be used to study the effect of test compounds on SLM-1 or SLM-2 deficiency.

Abstract: The present invention relates to pharmaceutical compositions, methods and kits that provide for the early diagnosis and treatment of breast cancer. More particularly, the present invention relates to pharmaceutical compositions containing uteroglobin for preventing or inhibiting metastasis of breast tumor cells and methods of using the same to prevent or inhibit metastasis of breast tumor cells. The present invention also relates to methods and kits for early diagnosis of metastatic breast cancer by assaying for uteroglobin and comparing the results against control cells. The present invention also relates to methods and kits for detection of metastatic breast cancer by assaying for the presence of an aberrant form of uteroglobin.

Abstract: A reagent for immunologically detecting rheumatism containing as an antigen at least one mammalian protein selected from among ezrin, radixin and moesin and/or a peptide composed of at least nine consecutive amino acid residues found in the amino acid sequences of ezrin, radixin and moesin; and a method of detecting autoantibodies present in the serum of a rheumatic. An immunological reaction using this reagent enables precritical or early diagnosis of rheumatism. An immunological detection using the above autoantigenic proteins is convenient and reliable as an early serodiagnostic method based on rheumatism-specific antigens.

Abstract: The invention relates to a process for in vitro diagnosis of an infection by human cytomegaloviruses. The process consists of contacting cells, possibly carrying the infection, with a monoclonal antibody reacting with a polypeptide of molecular weight 68,000, induced by human cytomagalovirus and which possesses a protein-kinase activity. The detection of the reaction is preferably carried out by immunofluorescence.

Abstract: A complex comprising a lipid and a conjugate of GPIb and lipid having a functional group, and use thereof. The GPIb-lipid complex of the present invention is extremely useful as a platelet substitute, a pharmaceutical agent for the prophylaxis and treatment of angiopathy, vascular damages and thrombosis, a diagnostic for vWF deficiency and the like, a biological or medical reagent, a reagent for screening platelet aggregation suppressant or antithrombosis, and the like. The GPIb-lipid complex of the present invention is also useful as a diagnostic for finding the location of vascular lesion or thrombus formation, or a therapeutic agent therefor, since it accumulates at vascular lesions.

Abstract: Modified proteins, modified interferons .alpha.'s and .beta.'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-.alpha.-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-.alpha.-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-.alpha.-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as E. coli. Numerous uses for the phosphorylated proteins are disclosed.

Abstract: The invention provides response regulator polypeptides and polynucleotides encoding response regulator polypeptides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing response regulator polypeptides to screen for antibacterial compounds.

Abstract: This invention relates in general to a phosphoprotein product of the retinoblastoma susceptibility gene. In particular, this invention relates to a phosphoprotein ppRB.sup.110 primarily located in the cell nucleus which has a DNA binding activity. The invention also relates to the amino acid sequence of the phosphoprotein and to the specific purified anti-retinoblastoma phosphoprotein antibody. The invention further relates to a method of diagnosing retinoblastoma and other retinoblastoma gene involved cancers, treating such kind of cancers and regulating the oncogenicity of other genes.

Abstract: The invention provides heterobifunctional cross-linking reagents and methods of using the cross-linking reagents. The cross-linking reagents of the invention combine a nucleophilic hydrazide residue with an electrophilic maleimide residue, allowing coupling of aldehydes to free thiols. In the methods of the invention, human immunodeficiency virus (HIV) infected cells can be detected using conjugates that include CD4 molecules conjugated to detectable markers via the disclosed cross-linking reagents.

Abstract: The present invention relates, in general, to a kinase which in its activated state is capable of site-specific phosphorylation of I.kappa.B.alpha., I.kappa.B.alpha. kinase. In particular, the present invention relates to the purified- kinase, purified polypeptide subunits of the kinase, nucleic acid molecules coding for the purified polypeptide subunits; recombinant nucleic acid molecules; cells containing the recombinant nucleic acid molecules; antibodies having binding affinity specifically to the kinase or its polypeptide subunits; hybridomas containing the antibodies; nucleic acid probes for the detection of the nucleic acid encoding the kinase; a method of detecting nucleic acids encoding the kinase or polypeptides of the kinase in a sample; and kits containing nucleic acid probes or antibodies. This invention further relates to bioassays using the nucleic acid sequence, protein or antibodies of this invention to diagnose, assess, or prognose a mammal afflicted with an undesired activation of NF-.kappa.

Abstract: This invention relates to phosphotyrosine mimics which, when incorporated into an appropriate molecular structure, are capable of inhibiting the binding of tyrosine kinase-dependent regulatory proteins to the native phosphotyrosine-containing receptors. This invention also relates to methods and kits for identifying and using phosphotyrosine mimics. The compounds, kits and methods of this invention are useful for identifying and designing antagonists of tyrosine-kinase dependent regulatory proteins, such as signal transduction proteins containing SH.sub.2 binding domains.

Abstract: This invention relates to drug binding proteins, to genes encoding same and to assays and methods for screening pharmaceuticals. More specifically, this invention relates to a Cytokine Suppressive Anti-Inflammatory Drug (CSAID) binding protein CSBP.beta., to a gene encoding same and to assays and screens useful in the evaluation and characterization of drugs of this pharmacologic class.

Abstract: The invention relates to a method for the renaturation of denatured proteins in which they are treated with a renaturant which has on vicinal carbon atoms a hydroxyl group and at least one fluorine atom.

Abstract: Modified proteins, modified interferons .alpha.'s and .beta.'s, phosphorylated modified proteins and DNA sequences encoding the above, applications and uses thereof. Modified phosphorylated Hu-IFN-.alpha.-like proteins are provided which carry an identifiable label such as a radio-label. Corresponding phosphorylatable Hu-IFN-.alpha.-like proteins which contain a putative phosphorylation site. DNA sequences which encode a Hu-IFN-.alpha.-like protein and contain a sequence encoding a putative phosphorylatable site. Appropriate expression vectors are used to transform compatible host cells of various microorganisms, such as E. coli. Numerous uses for the phosphorylated proteins are disclosed.

Abstract: Novel PMP, PME and HPMP and related compounds containing N-6 substituted 2,6-diaminopurine and adenine bases are provided. These compounds are useful in a variety of utilities, including as intermediates in the preparation of flame retardants, diagnostic reagents and therapeutics, including antivirals. Of particular note are compounds otherwise not known to possess anti-DNA viral activity that become potent inhibitors of DNA viruses upon substitution of the N-6 site, thereby providing a novel and unexpected and surprising use for such compounds.

Abstract: Compositions and methods are provided for treating NF-.kappa.B-related conditions. In particular, the invention provides a stimulus-inducible I.kappa.B.alpha. kinase complex, and components and variants thereof. I.kappa.B.alpha. kinase complex may be used, for example, to identify antibodies and other agents that inhibit or activate signal transduction via the NF-.kappa.B cascade. I.kappa.B.alpha. kinase complex, components thereof and/or such agents may also be used for the treatment of diseases associated with NF-.kappa.B activation.

Abstract: Novel gene, rin2, and encoded protein are disclosed which can inhibit the functional response induced by Ras-dependent signaling pathways are disclosed. Methods of inhibiting or enhancing Ras-dependent signaling and methods of treatment utilizing Rin2 are also disclosed.

Abstract: The invention relates to a homeoprotein regulator of insulin gene expression having the characteristics of: binding to an element of an insulin gene promoter; being modulated by a Ca.sup.++ -dependent CaM kinase IV; and having homology to a nucleotide sequence encoded by a Hox gene complex. Also included within the invention are DNA sequences encoding the homeoprotein regulators of insulin gene expression, antibodies directed to the homeoprotein regulators of insulin gene expression, and diagnostic and therapeutic materials and utilities for the homeoprotein regulators of insulin gene expression.

Abstract: A novel protein tyrosine phosphatase designated PTP-S31 and its subfamily are identified, as are nucleic acid molecule coding therefor. Included in this family are PTP-S31 proteins or glycoproteins having one, two, or three identified amino acid changes in previously defined consensus sequences in the catalytic phosphatase domains of known protein tyrosine phosphatases. The PTP-S31 proteins or glycoproteins may be produced by recombinant means. Antibodies to PTP-S31 proteins or glycoproteins and nucleic acid constructs coding therefor, and methods for screening molecules which can bind to PTP-S31 proteins or glycoproteins and inhibit or stimulate their enzymatic activity, are provided.

Abstract: Compositions and methods are provided for the treatment of diseases associated with mitogen activated protein kinase cascades. In particular, the mitogen-activated protein kinase p38-2, and polypeptide variants thereof that stimulate phosphorylation and activation of substrates such as ATF2, are provided. The polypeptides may be used, for example, to identify antibodies and other agents that inhibit or activate signal transduction via the p38-2 kinase cascade. Such polypeptides and agents may also be used for the treatment of diseases associated with mitogen-activated protein kinase cascades.

Abstract: A lipoprotein particle and a therapeutic lipoprotein composition are disclosed. The lipoprotein particle consists essentially of lecithin phospholipids with low phase transition temperatures and human apoproteins A and C. A therapeutic composition for therapeutic administration to a subject, comprising the lipoprotein particles of the invention, is also disclosed. The composition is useful is treating disease conditions associated with elevated serum Lp(a) levels, as well as hypertension and acute renal failure.

Abstract: Novel receptor polypeptides, polynucleotides encoding the polypeptides, and related compositions and methods are disclosed. The polypeptides comprise an extracellular ligand-binding domain of a cell-surface receptor that is expressed at high levels in lymphoid tissue, including B-cells and T-cells. The polypeptides may be used within methods for detecting ligands that stimulate the proliferation and/or development of lymphoid and myeloid cells in vitro and in vivo. Ligand-binding receptor polypeptides can also be used to block ligand activity in vitro and in vivo.

Abstract: The invention provides Response Regulator polypeptides and DNA (RNA) encoding Response Regulator polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Response Regulator polypeptides to screen for antibacterial compounds.

Abstract: This invention provides assays for protein kinase activity using fluorescent proteins engineered to include sequences that can be phosphorylated by protein kinases. The proteins exhibit different fluorescent properties in the non-phosphorylated and phosphorylated states.

Abstract: The invention provides Response regulator polypeptides and DNA (RNA) encoding Response regulator polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Response regulator polypeptides to screen for antibacterial compounds.

Abstract: The invention provides Response Regulator polypeptides and DNA (RNA) encoding Response Regulator polypetides and methods for producing such polypeptides by recombinant techniques. Also provided are methods for utilizing Response Regulator polypeptides to screen for antibacterial compounds.

Abstract: Three mammalian are disclosed which are useful in the diagnosis and prognosis of tumors of lymphoid and epithelial origin. The three proteins are immunologically related to each other. The level of expression of the proteins correlates with the malignant potential of lymphoid and epithelial tumors. In addition, in some cases the subcellular location of the proteins is indicative of malignant potential. Antibodies reactive with the proteins are disclosed as diagnostic tools, as are nucleic acid probes and primers for quantitating the messenger RNAs encoding the proteins. Methods for preparing and purifying the proteins are also taught.

Abstract: This invention relates to drug binding proteins, to genes encoding same and to assays and methods for screening pharmaceuticals. More specifically, this invention relates to a Cytokine Suppressive Anti-Inflammatory Drug (CSAID) binding protein CSBP.beta., to a gene encoding same and to assays and screens useful in the evaluation and characterization of drugs of this pharmacologic class.

Abstract: A novel expression cloning method is provided for the detection, identification and purification of target proteins capable of binding at least to a tryosine-phosphorylated domain of a eukaryotic tyrosine kinase using novel peptide probes comprising an amino acid sequence substantially corresponding to a portion of a tyrosine-phosphorylated domain of a tyrosine kinase. The probe has at least one phosphorlated tyrosine residue and may be detectably labeled. Also disclosed is a method for preparing the probe, a method for mapping to a chormosome a gene encoding a protein capable of binding to tyrosine-phosphorylated domains of tyrosine kinases, and a method for purifiying such a protein with the probe. Non-limiting examples of novel proteins discovered using the above cloning method include GRB-1, GRB-2, GRB-3, GRB-4 and GRB-7, as well as nucleic acid encoding these proteins, and methods for detecting these proteins are also provided.

Abstract: Methods of generating a rat having A.beta. deposits in the brain of the rat by injecting an amount of human A68 protein sufficient to result in formation of the deposits and subsequently examining the rat for the formation of the deposits are disclosed. Rats characterized by the presence of A.beta. deposits similar to those found in individuals with Alzheimer's disease are also disclosed. Methods of screening test compositions for prophylactic or therapeutic activity by generating a rat having A.beta. deposits in its brain, treating the animal with the test composition and examining the animal for therapeutic or prophylactic effectiveness are also disclosed.

Abstract: The phosphorylated structural protein of molecular weight about 150 kd (pp 150) of human cytomegalovirus (HCMV) is highly immunogenic and is reliably recognised by human antisera. This protein can, after assignment and sequencing of the gene, be prepared, in whole or in immunogenic sections, by gene manipulation. Proteins of this type are suitable as reagents, for example in an ELISA, and as constituents of vaccines.

Abstract: Phosphopeptides which significantly reduce bone loss or weakening are provided by the invention. Also provided is a method for treating or preventing any condition associated with bone loss or weakening by administering the phosphopeptides by oral or injectable means.

Abstract: A chimeric compound that contains a cell-specific ligand linked to a pore-forming agent capable of lysing a cell.

Abstract: An assay for screening test compounds to indentify agents which modulate the binding of an E6-BP polypeptide with a papilloma virus E6 protein. The assay includes combining, as a cell-free system, an E6-binding protein or fragment thereof which binds to the E6 protein, and a test compound, and detecting the formation of a complex which includes the E6 protein and the E6-binding protein. A change in the formation of the complex in the presence of the test compound is indicative of an agent that modulates interaction between an E6 and an E6-binding protein.

Abstract: A method for assaying a medium for the presence of a substance that affects an SH2-phosphorylated ligand regulatory system. The method employs an SH2-like domain or a subdomain thereof and a phosphorylated ligand. The phosphophorylated ligand is capable of interacting with the SH2-like domain or a subdomain thereof to form an SH2-phosphorylated ligand complex. The SH2-like domain or subdomain and/or the phosphorylated ligand are present in a known concentration. The SH2-like domain or a subdomain thereof and the phosphorylated ligand are incubated with a substance which is suspected of affecting an SH2-phosphorylated ligand regulatory system. The method is carried out under conditions which permit the formation of the SH2-phosphorylated ligand complex. SH2-phosphorylated ligand complex, free SH2-like domain or subdomains thereof, or non-complexed phosphorylated ligand are assayed.

Abstract: Described are cloning and sequencing of genes encoding novel isoforms (paxillins .beta. and .gamma.) of focal adhesion protein paxillin. According to the present invention, there is provided a novel gene for an isoform of focal adhesion protein paxillin. This gene is useful medical applications such as diagnosis of progress of cancer malignancy, development of a drug (cancer treatment) for preventing the metastasis and infiltration of cancer cells, etc.

Abstract: This invention relates to the isolation, identification and sequencing of a cancer associated protein, preparation of hybridization probes therefrom, preparation of antibodies thereto, and methods of cancer risk assessment and diagnosis.

Abstract: The present invention is based on the identification and sequence determination of a novel gene, ALK, which is fused to the gene encoding nucleophosmin (NPM) in translocations present in t(2;5) lymphoma cells. Based on homologies to other proteins, the amino acid sequence of the polypeptide encoded by the ALK (Anaplastic Lymphoma Kinase) gene is a membrane-spanning protein tyrosine kinase (PTK)/receptor. Antibodies to the ALK PTK/receptor and methods utilizing such antibodies are described, as are methods of using the ALK gene to isolate ligands for the ALK PTK/receptor.

Abstract: Disclosed is a method of evaluating an anti-proliferative compound by contacting the compound with a Raf and determining its ability to bind to Ras, and methods of inhibiting cell proliferation in an animal by administering a compound which reduces the interaction of Ras with Raf.

Abstract: Three mammalian are disclosed which are useful in the diagnosis and prognosis of tumors of lymphoid and epithelial origin. The three proteins are immunologically related to each other. The level of expression of the proteins correlates with the malignant potential of lymphoid and epithelial tumors. In addition, in some cases the subcellular location of the proteins is indicative of malignant potential. Antibodies reactive with the proteins are disclosed as diagnostic tools, as are nucleic acid probes and primers for quantitating the messenger RNAs encoding the proteins. Methods for preparing and purifying the proteins are also taught.